Device and method for auditory stimulation

ABSTRACT

A device and method for desynchronizing a patient&#39;s neuronal brain activity in which the neuron population is firing in a pathologically synchronized manner. The device includes a stimulation unit that generates an acoustic stimulation signal that includes both a first tone and a second tone. The first tone is provided to shift the phase of the neuronal brain activity of a first subpopulation of the neuron population relative to the phase of the neuronal brain activity of a second subpopulation of the neuron population when the first tone is acoustically received by the patient. Further, the second tone is provided to shift the phase of the neuronal brain activity of the second subpopulation relative to the phase of the neuronal brain activity of the first subpopulation when the second tone is acoustically received by the patient. As a result, the acoustic stimulation signal desynchronizes the stimulated neuron population.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.13/796,422, filed Mar. 12, 2013, which is a continuation of U.S.application Ser. No. 12/884,557, filed Sep. 17, 2010, which claimspriority to International Application No. PCT/DE2009/000399, filed Mar.20, 2009, which claims priority to German Application No. 10 2008 015259.5, filed Mar. 20, 2008, the entire contents of each of which areincorporated herein by reference.

BACKGROUND

There are excessively strong neuronal activity synchronizationprocedures in the brain in a number of neurological and psychiatricdiseases and these have a very strong negative influence on the cerebralfunction. Tinnitus is such a disease. Tinnitus refers to a sound in theear, mostly in the form of a high-pitched tone, but occasionally alsohaving a knocking, pulsing or beating character. It is a widespreaddisease in the form of disturbing sensations that are of an agonizingnature for many patients. Currently available therapy methods for suchdiseases include pharmacotherapy, deep brain stimulation and the like.

SUMMARY

The present application is directed to a device and method fordesynchronizing a patient's neuronal brain activity involving a neuronpopulation firing in a pathologically synchronized manner. The deviceincludes a stimulation unit configured to generate an acousticstimulation signal to stimulate the neuron population when the acousticstimulation signal is aurally received by the patient. Furthermore, theacoustic stimulation signal has a first frequency and a secondfrequency, with the first frequency provided to reset the phase of theneuronal brain activity in a first sub-population of the stimulatedneuron population, and the second frequency provided to reset the phaseof the neuronal brain activity in a second sub-population of thestimulated neuron population.

In another aspect of the present application, a device is provided fordesynchronizing a patient's neuronal brain activity involving a neuronpopulation firing in a pathologically synchronized manner. In thisaspect, the device includes a stimulation unit to generate an acousticstimulation signal to stimulate the neuron population when the acousticstimulation signal is aurally received by the patient; a measurementunit to record a measurement signal on a patient, which measurementsignal reproduces the neuronal activity in the auditory cortex of thepatient or a region connected thereto; and a control unit to actuate thestimulation unit based on the measurement signal such that thestimulation unit converts the measurement signal into the acousticstimulation signal.

In further aspect of the present application, a method is provided fordesynchronizing a patient's neuronal brain activity involving a neuronpopulation firing in a pathologically synchronized manner, the methodincluding generating an acoustic stimulation signal to stimulate theneuron population when the acoustic stimulation signal is aurallyreceived by the patient, the acoustic stimulation signal having at leasta first frequency and a second frequency; setting the first frequency toreset the phase of the neuronal brain activity in a first sub-populationof the stimulated neuron population; and setting the second frequency toreset the phase of the neuronal activity in a second sub-population ofthe stimulated neuron population.

In yet a further aspect of the application, a method is provided fordesynchronizing a patient's neuronal brain activity involving a neuronpopulation firing in a pathologically synchronized manner. In thisaspect, the method includes recording a measurement signal on a patient,which measurement signal reproduces the neuronal activity in theauditory cortex or a region connected thereto; converting themeasurement signal into an acoustic stimulation signal; and generatingthe acoustic stimulation signal to stimulate the neuron population whenthe acoustic stimulation signal is aurally received by the patient.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a schematic illustration of a device 100 as per anexemplary embodiment.

FIG. 2 shows an illustration of sinusoidal oscillations at thefrequencies of f₁, f₂, f₃ and f₄ as per an exemplary embodiment.

FIG. 3 shows an illustration of a sinusoidal oscillationamplitude-modulated by a rectangular function as per an exemplaryembodiment.

FIG. 4 shows a schematic illustration of a device 400 as per a furtherexemplary embodiment.

FIG. 5 shows a schematic illustration of a device 500 as per a furtherexemplary embodiment.

FIG. 6 shows a schematic illustration of a device 600 as per a furtherexemplary embodiment.

FIG. 7 shows a schematic illustration of a device 700 as per a furtherexemplary embodiment.

FIG. 8 shows a schematic illustration of a device 800 as per a furtherexemplary embodiment.

FIG. 9 shows a schematic illustration of a device 900 as per a furtherexemplary embodiment.

FIG. 10 shows a schematic illustration of an auditory stimulation methodas per an exemplary embodiment.

FIG. 11 shows a schematic illustration of a further auditory stimulationmethod as per an exemplary embodiment.

FIG. 12 shows a schematic illustration of a further auditory stimulationmethod as per an exemplary embodiment.

FIG. 13 shows a schematic illustration of a further auditory stimulationmethod as per an exemplary embodiment.

FIG. 14 shows a schematic illustration of a further auditory stimulationmethod as per an exemplary embodiment.

FIG. 15A and 15B show schematic illustrations of the generation ofmodulation signals as per an exemplary embodiment.

DETAILED DESCRIPTION

FIG. 1 illustrates in a schematic fashion a device 100, which consistsof a control unit 10 and a stimulation unit 11 connected to the controlunit 10. FIG. 1 furthermore illustrates an ear 12 of a patient and theauditory cortex 13 in the brain of the patient in a schematic fashion.

The stimulation unit 11 is actuated by the control unit 10 by means ofone or more control signals 14 during the operation of the device 100,and the stimulation unit 11 generates one or more acoustic stimulationsignals 15 with the aid of the control signal 14. The frequency spectrumof the acoustic stimulation signal 15 may lie completely or partly inthe range audible to a human. The acoustic stimulation signal 15 istaken in by the patient by one or both ears 12 and is transmitted toneuron populations in the brain via the cochlear nerve or nerves 16. Theacoustic stimulation signal 15 is developed such that it stimulatesneuron populations in the auditory cortex 13. At least a first frequencyf₁ and a second frequency f₂ are present in the frequency spectrum ofthe acoustic stimulation signal 15. The acoustic stimulation signal 15can furthermore contain additional frequencies or frequency mixtures; inthe exemplary embodiment shown in FIG. 2, these are a third frequency f₁and a fourth frequency f₄.

The device 100 can be used in particular for treating neurological orpsychiatric diseases, such as tinnitus, migraine, headaches of differentform and genesis (e.g. cluster headache), trigeminal neuralgia, sleepdisorders, neuralgias and headaches in the case of neuroborreliosis,attention deficit syndrome (ADS), attention deficit hyperactivitysyndrome (ADHS), neuroses, compulsion neuroses, depressions, mania,schizophrenia, tumors, arrhythmias, addiction diseases, bruxism(nocturnal teeth grinding), eating disorders, and the like.

The aforementioned diseases can be caused by a disorder in thebioelectric communication of neural networks connected in specificcircuits. Herein, a neuron population continuously generatespathological neuronal activity and possibly a pathological connectivity(network structure) associated therewith. In the process, a large numberof neurons form action potentials at the same time, i.e. the involvedneurons fire in an overly synchronous fashion. Additionally, the sickneuron population exhibits an oscillatory neuronal activity, i.e. theneurons fire rhythmically. In the case of the aforementioned diseases,the mean frequency of the pathological rhythmic activity of the affectedneural networks lies approximately in the range between 1 and 30 Hz, butit can also lie outside of this range. The neurons fire qualitativelydifferently in healthy humans, e.g. in an uncontrolled fashion.

The acoustic stimulation signal 15 generated by the stimulation unit 11is converted into nerve impulses in the inner ear and transmitted to theauditory cortex 13 via the cochlear nerve 16. The tonotopic arrangementof the auditory cortex 13 means that a particular part of the auditorycortex 13 is activated in the case of the acoustic stimulation of theinner ear with a particular frequency. The tonotopic arrangement of theauditory cortex is described, for example, in the following articles:“Tonotopic organization of the human auditory cortex as detected byBOLD-FMRI” by D. Bilecen, K. Scheffier, N. Schmid, K. Tschopp and J.Seelig (published in Hearing Research 126, 1998, pages 19 to 27),“Representation of lateralization and tonotopy in primary versussecondary human auditory cortex” by D. R. M. Langers, W. H. Backes andP. van Dijk (published in NeuroImage 34, 2007, pages 264 to 273) and“Reorganization of auditory cortex in tinnitus” by W. Mülnickel, T.Elbert, E. Taub and H. Flor (published in Proc. Natl. Acad. Sci. USA 95,1998, pages 10340 to 10343).

In the example as per FIG. 1, the acoustic stimulation signal 15 isdeveloped such that it stimulates a neuron population in the auditorycortex 13 with a pathologically synchronous and oscillatory activity.Before the stimulation is initiated, this neuron population can at leastbe thought of being subdivided into various sub-populations, inter ciliathe sub-populations 17, 18, 19 and 20 shown in FIG. 1. Before thestimulation is initiated, the neurons of all sub-populations 17 to 20for the most part fire synchronously and on average with the samepathological frequency. Due to the tonotopic organization of theauditory cortex 13, the first sub-population 17 is stimulated by meansof the first frequency f₁, the second sub-population 18 is stimulated bymeans of the second frequency f₂, the third sub-population 19 isstimulated by means of the third frequency f₃ and the fourthsub-population 20 is stimulated by means of the fourth frequency f₄. Thestimulation by the acoustic stimulation signal 15 brings about aresetting, a so-called reset, of the phase of the neuronal activity inthe stimulated neurons in the respective sub-populations 17 to 20. Thereset sets the phase of the stimulated neurons to a certain phase value,e.g. 0°, independently of the current phase value. Hence the phase ofthe neuronal activity of the pathological sub-populations 17 to 20 iscontrolled by means of a targeted stimulation.

The pathological neuron population can be stimulated in a targetedfashion at the different sites 17 to 20 as a result of the tonotopicarrangement of the auditory cortex 13 and the plurality of frequenciesf₁ to f₄ contained in the acoustic stimulation signal 15. This affordsthe possibility of resetting the phase of the neuronal activity of thepathological neuron population at different times at the differentstimulation sites 17 to 20 by applying the frequencies f₁ to f₄ atdifferent times. As a result, this subdivides the pathological neuronpopulation, the neurons of which were previously active in a synchronousfashion and with the same frequency and phase, into the sub-populations17 to 20. Within each of the sub-populations 17 to 20, the neurons arestill synchronous and also on average still fire with the samepathological frequency, but each of the sub-populations 17 to 20 has thephase in respect of its neuronal activity that was imposed on it by thestimulation stimulus with the associated frequency f₁ to f₄.

Due to the pathological interaction between the neurons, the state withat least two sub-populations, which state was generated by thestimulation, is unstable and the entire neuron population quicklyapproaches a state of complete desynchronization, in which the neuronsfire in an uncorrelated fashion. The desired state, i.e. the completedesynchronization, thus is not available immediately after theapplication of the acoustic stimulation signal 15 via the stimulationunit 11, but usually sets in within a few periods or even within lessthan one period of the pathological activity.

In the type of stimulation described above, the ultimately desireddesynchronization is only made possible by the pathologically increasedinteraction between the neurons. Hereby, a self-organization process isutilized, which is responsible for the pathological synchronization. Thesame process brings about a desynchronization following a subdivision ofan entire population into sub-populations with different phases,

Moreover, the stimulation with the device 100 can obtain areorganization of the connectivity of the dysfunctional neural networksand so long-lasting therapeutic effects can be brought about, which lastsignificantly longer than the acoustic stimulation.

In order to stimulate the auditory cortex 13 at different sites focally,e.g. the sites or sub-populations 17 to 20 shown in FIG. 1, pure tonesof the associated frequencies f₁, f₂, f₃ and f₄ have to be dispensed. Asa result of the tonotopic arrangement of the auditory cortex 13,different parts of the brain are stimulated by the simultaneousdispensation of the associated various pure tones f₁ to f₄, i.e. by thesuperposition of various sinusoidal oscillations. If the four differentsites 17 to 20 are intended to be stimulated e.g. at different times,the four different frequencies f₁ to f₄ are applied at the respectivetimes. This is shown in an exemplary fashion in FIG. 2. Here sinusoidaloscillations at the frequencies f₁=1000 Hz, f₂=800 Hz, f₃=600 Hz andf₄=400 Hz are applied successively and as pulses, which leads to asuccessive focal stimulus at the four different sites 17 to 20 in theauditory cortex 13. The strength of the stimulus of the respective areain the auditory cortex 13 generated by the respective sinusoidaloscillation corresponds to the amplitude of the respective sinusoidaloscillation.

The generation of the pulsed sinusoidal oscillations shown in FIG. 2 isillustrated in FIG. 3 in an exemplary fashion. There, a sinusoidaloscillation 21 is multiplied by a rectangular function 22, which can forexample assume the values 0 or 1. At the times at which the rectangularfunction 22 has a value of 0 the associated stimulus is switched off andwhile the rectangular function 22 equals 1 the stimulus is switched on.The sinusoidal oscillation 21 can be multiplied by any other functioninstead of the rectangular function 22. As a result this multiplicationcorresponds to an amplitude modulation of the sinusoidal oscillation 21.

Alternatively, instead of the above-described sinusoidal oscillations,use can also be made of oscillating signals with a different signalform, e.g. rectangular signals oscillating with the corresponding basefrequency, for generating the acoustic stimulation signal 15.

Provided that a less focal stimulation that activates relatively largeparts of the auditory cortex 13 is intended to be carried out instead ofa focal stimulation, frequency mixtures are applied, e.g. in a pulsedfashion, instead of individual frequencies. Using a frequency mixturebounded between a lower frequency f^(lower) and an upper frequencyf^(upper) stimulates all those parts of the auditory cortex 13 that arestimulated by the frequencies between f^(lower) and f^(upper) due to thetonotopic arrangement. If, for example, four different, relatively largeregions of the auditory cortex 13 are intended to be stimulated atdifferent times, the four associated frequency mixtures with theboundaries f_(j) ^(lower) and f_(j) ^(upper) (j=1, 2, 3, 4) are appliedat the desired times.

In the exemplary embodiment, the device 100 can be operated in aso-called “open-loop” mode, in which the control unit 10 actuates thestimulation unit 11 such that the latter generates prescribed acousticstimulation signals 15 during a defined stimulation time (e.g. over aplurality of hours). Moreover, the device 100 can also be developed toform a device 400 shown in FIG. 4, the latter device constituting aso-called “closed-loop” system. In addition to the components known fromFIG. 1, the device 400 also contains a measurement unit 23, whichprovides one or more measurement signals 24 recorded on the patient andtransmits said signals to the control unit 10. In a refinement of thisembodiment, provision can be made for the control unit 10 to actuate thestimulation unit 11 on the basis of the measurement signals 24 recordedby the measurement unit 23. The measurement unit 23 can involvenon-invasive sensors, such as electroencephalography (EEG) electrodes,magnetoencephalography (MEG) sensors, accelerometers, electromyography(EMG) electrodes and sensors for determining blood pressure, respirationor skin resistance. Furthermore, the measurement unit 23 in the form ofone or more sensors can be implanted into the body of the patient. Byway of example, epicortical, intracortical or subcutaneous electrodescan be used as invasive sensors. In particular, the measurement unit 23can be used to measure the physiological activity in the stimulatedtarget region or in a region connected therewith.

Various refinements are feasible in respect of the interaction of thecontrol unit 10 with the measurement unit 23. By way of example, thecontrol unit 10 can perform a demand-driven stimulation. For this, thecontrol unit 10 detects the presence and/or the development of one ormore pathological features on the basis of the measurement signals 24recorded by the measurement unit 23. By way of example, the amplitude orthe magnitude of the neuronal activity can be measured and compared to apredetermined threshold. The control unit 10 can be configured such thatstimulation of one or more target areas in the auditory cortex isinitiated as soon as the prescribed threshold is exceeded. Furthermore,parameters of the acoustic stimulation signals 15, such as theamplitudes of the respective sinusoidal oscillations or the pausesbetween stimulation sequences, can be set by the control unit 10 on thebasis of the development of the pathological features. By way ofexample, one or more thresholds can be prescribed, and if the amplitudeor the magnitude of the measurement signals 24 exceeds or drops below acertain threshold, the control unit 10 varies a particular parameter ofthe acoustic stimulation signal 15, such as the amplitude of one or moresinusoidal oscillations from which the acoustic stimulation signal 15 iscomposed.

In a further refinement, provision can be made for the measurementsignals 24 recorded by the measurement unit 23 to be converted directlyor if need be after one or more processing steps into acousticstimulation signals 15 and to be applied by the stimulation unit 11. Byway of example, the measurement signals 24, amplified and if need beafter mathematical combination (e.g. after mixing the measurementsignals) with a time delay and linear and/or nonlinear combinationsteps, can be fed as control signals into the control input of thestimulation unit 11. Herein, the combination mode is selected such thatthe pathological neuronal activity is counteracted and the acousticstimulation signals 15 likewise disappear or are at least significantlyreduced in strength (amplitude) as the pathological neuronal activityreduces.

FIG. 5 schematically illustrates a device 500 that constitutes adevelopment of the device 100 shown in FIG. 1. In the exemplaryembodiment, there is no need to implant any component of the device 500,and so the entire device 500 is located outside of the body of thepatient. Moreover, in this embodiment, the device 500 does not use anysignal measured by a sensor for the demand-driven variation of thestimulation. A sound generator (loudspeaker) is used as a stimulationunit 11 in the device 500, which sound generator is surrounded by anearplug 30. The earplug 30 is inserted into the outer auditory canal ofan ear 12 of the patient and attached to the ear 12 with or without aholder or another suitable mechanical aid. The control unit 10, whichactuates the sound generator, and also a battery or a rechargeablebattery for supplying the electrical components of the device 500 withcurrent can be housed in one or more separate units 31. The unit 31 canbe connected to the earplug 30 by means of a mechanical fastener, e.g. aholder. A connection cable 32 connects the earplug 30 to the controlunit 10 and the battery.

Alternatively, headphones containing the control unit 10 and the batterycan also be used instead of the earplug 30. The device 500 can beswitched on by the patient by means of an operating unit (e.g. switch-onbutton and/or control dial), which is attached either to the unit 31 ordirectly to the earplug 30. The control dial can be used, for example,to set the maximum stimulation strength. In addition to theaforementioned components, the device 500 can comprise a control medium33, which for example is connected to the control unit 10 in atelemetric fashion (e.g. by radio waves) or by means of a connectioncable. In the case of a cabled connection, plug-in connections can beused for connection and disconnection.

Furthermore, the device 500 can also comprise an additional controlmedium (not illustrated) operable by e.g. the medical practitioner,which control medium is connected to the control unit 10 in a telemetricfashion or by means of a connection cable. In the case of a cabledconnection, plug-in connections can be used for connection anddisconnection.

Moreover, one or more sensors, such as. EEG electrodes or anaccelerometer or the like, can be provided for registering and/ordocumenting the stimulation success or for the examination by themedical practitioner.

FIGS. 6 to 9 schematically illustrate devices 600, 700, 800 and 900 asdevelopments of the device 400. The devices 600 to 900 in each casecomprise a measurement unit 23, by means of which demand-driven controlcan be performed and/or the measurement signals 24 can be fed back intothe stimulation unit 11. In this case, the devices 600 and 700constitute non-invasive variants, while the devices 800 and 900 arepartly implanted into the body of the patient. Like the device 500, thedevices 600 to 900 comprise an earplug 30 or headphones with a soundgenerator.

In addition to the above-described components of the device 500, thedevice 600 illustrated in FIG. 6 comprises epicutaneous, i.e. attachedto the skin of the patient, EEG electrodes 34 that are connected to thecontrol unit 10 in the unit 31 via connection cables 35, 36. The controlunit 10 amplifies the potential difference measured by means of the EEGelectrodes 34 and uses said potential difference for actuating the soundgenerator in the earplug 30 after an optional linear or nonlinearcombination. As an alternative to the connection cables 35, 36, the EEGelectrodes 34 can also be connected wirelessly, i.e. telemetrically, tothe control unit 10. The advantage of this is that the patient is notimpeded by connection cables and can not be caught in obstacles, forexample,

The device 700 illustrated in FIG. 7 has an accelerometer 37 as ameasurement unit instead of an EEG electrode. The accelerometer 37 isattached, like a watch, to a limb of the patient that trembles due todisease. The acceleration signals recorded by the accelerometer 37 areamplified in the control unit 10 and are used for actuating the soundgenerator in the earplug 30 after an optional linear or nonlinearcombination. The accelerometer 37 can be connected to the control unit10 in a telemetric fashion or by means of a connection cable.

FIG. 8 shows an invasive variant. In the illustrated exemplaryembodiment, the device 800 comprises one or more subcutaneouslyimplanted electrodes 38 as a measurement unit, a connection cable 39 anda transmission and reception unit 40, which are implanted into the bodyof the patient under the scalp 41 and outside of the bony skull 42.Outside of the body of the patient there is a transmission and receptionunit 43, which is connected to the unit 31 and the control unit 10situated therein via a connection cable 44. The measurement signals 24recorded by the electrode 38 are transmitted to the control unit 10 viathe transmission and reception units 40 and 43, which for example areeach implemented as a coil and which allow the wireless andbidirectional transmission of signals and electrical power therebetween.The potential differences measured by the electrode 38 are amplified inthe control unit 10 and are used for actuating the sound generatorintegrated into the earplug 30 after an optional linear or nonlinearcombination.

A further invasive variant is illustrated schematically in FIG. 9. Oneor more epicortically implanted electrodes 45 serve as a measurementunit in the device 900 shown therein. One skilled in the art understandthat “epicortical” means “situated on the cerebral cortex.” As shown inFIG. 9, the cerebral cortex 46, 47 of both hemispheres is shownschematically for illustrative purposes. The control unit 10 amplifiesthe potential difference measured by means of the epicorticallyimplanted electrode 45 and uses said potential difference for actuatingthe sound generator in the earplug 30 after an optional linear ornonlinear combination.

The epicortical electrode 45 shown in FIG. 9 can for example also bereplaced by an intracortical electrode (not illustrated).

The measurement signals recorded by the differently developedmeasurement units 23, i.e. the EEG-electrodes 34, the accelerometer 37or the electrodes 38 or 45, can be used for feed-back control, as willbe described in still more detail further below, and in one embodimentcan be fed into the sound generator as actuation signals. Alternatively,demand-driven control can be carried out on the basis of the measurementsignals 24. In the case of a stimulation targeted at resetting theneuronal phases of neuron sub-populations, certain parameters of thestimulation method, such as the stimulation strength or the stimulationduration, can be set with the aid of the measurement signals 24. Thistype of demand-driven control will be explained in still more detailfurther below in conjunction with FIGS. 10 to 12.

The four frequencies f₁ to f₄ are intended to be used below to explainin an exemplary fashion as to how a time-offset reset of the phases ofthe neuronal activity of sub-populations of a pathologically synchronousand oscillatory neuron population can achieve a desynchronization of theentire neuron population. The four frequencies f₁ to f₄ should merely beunderstood as exemplary, and it should be understood that any othernumber of frequencies or frequency mixtures can be used for stimulationpurposes. The frequencies f₁ to f₄ have been selected such that they ineach case stimulate particular regions 17 to 20 of the auditory cortex13. This affords the above-described subdivision of a pathologicalneuron population into sub-populations 17 to 20. In order for thesub-populations 17 to 20 to have different phases after the stimulation,the frequencies f₁ to f₄ can for example be applied with a time offset.

A stimulation method that is suitable for the above-described purposesand can for example be performed by one of the devices 100 to 900 isillustrated schematically in FIG. 10. The upper four rows of FIG. 10plot, one below the other, four sinusoidal oscillations with frequenciesf₁, f₂, f₃ and f₄ over time t. The acoustic stimulation signal 15 isformed from the illustrated sinusoidal oscillations. The four sinusoidaloscillations have been multiplied by rectangular functions forgenerating pulsed sinusoidal oscillations. Each sinusoidal oscillationpulse is repeated periodically with a frequency f_(stim). The frequencyf_(stim)=1/T_(stim) preferably lies in the range between 1 and 30 Hz andmore particularly in the range between 5 and 20 Hz, but it can alsoassume smaller or greater values as should be understood to one skilledin the art. Such sequences of pulsed sinusoidal oscillations aresuitable for resetting the neuronal phase of the respectively stimulatedpathological neuron sub-population 17, 18, 19 or 20 if said oscillationsare applied as acoustic stimulation signals 15. Here the phase resetdoes not necessarily already result after one or a few pulses, but acertain number of the sinusoidal oscillation pulses shown in FIG. 10 maybe required to reset the neuronal phase of the respective sub-population17, 18, 19 or 20.

By way of example, the frequency f_(stim) can lie in the vicinity of themean frequency of the pathologically rhythmic activity of the targetnetwork. In the case of neurological and psychiatric diseases, the meanfrequency typically lies in the range between 1 and 30 Hz, but it canalso lie outside of this range as noted above. In the case of tinnitus,there is overly synchronous neuronal activity in, for example, thefrequency range between 1.5 and 4 Hz. It should be noted herein that thefrequency at which the pathological neurons fire synchronously isusually not constant, but can by all means have variations and moreoverhas individual deviations in each patient.

The mean peak frequency of the pathological rhythmic activity of thepatient can for example be determined in order to calculate thefrequency f_(stim). This peak frequency can then be used as stimulationfrequency f_(stim) or else be varied, for example in a range betweenf_(stim)−3 Hz and f_(stim)+3 Hz. However, alternatively it is alsopossible for a frequency f_(stim) to be selected in the range between 1and 30 Hz without a preceding measurement and this frequency can forexample be varied during the stimulation until the frequency t_(stim) isfound, by means of which the best stimulation successes can be obtained.As a further alternative, a known value found in the literature for therespective disease can be used for the stimulation frequency f_(stim).If need be, this value can still be varied until for example optimumstimulation results are obtained.

The duration of a sinusoidal oscillation pulse, i.e. the period of timeduring which the rectangular function assumes a value of 1 in thepresent refinement, can for example be T_(stim)/2. In this case, theperiod of time during which the respective frequency contributes to thestimulation and the subsequent stimulation pause have the same length.However, other stimulation durations can also be selected, for examplein the range between T_(stim)/2−T_(stim)/10 and T_(stim)/2+T_(stim)/10.Other stimulation times are also possible, for example, the stimulationduration is T_(stim)/4 in the stimulations shown in FIGS. 11 and 12. Thestimulation durations can for example be determined experimentally.

According to the refinement shown in FIG. 10, the individual frequenciesf₁ to f₄ are dispensed with a time delay between the individualfrequencies f₁ to f₄. By way of example, the beginning of temporallysuccessive pulses having different frequencies can be offset by a timeτ.

In the case where N frequencies are used for the stimulation, the timedelay τ between two respectively successive pulses can for example liein the vicinity of an N-th of the period T_(stim)=1/f_(stim). In theexemplary embodiment (N=4) shown in FIG. 10, the time delay rcorrespondingly is T_(stim)/4. In one embodiment, there can be a certainamount of deviation from the specification that the time delay τ betweentwo respectively successive sinusoidal oscillation pulses is T_(stim)/N.By way of example, there can be a deviation of up to ±10%, ±20% or ±30%from the value T_(stim)/N for the time delay τ. Stimulation successeswere still obtained in the case of such a deviation, i.e. adesynchronizing effect could still be observed.

In the exemplary embodiment, the acoustic stimulation signal 15 isformed by superposition of the periodic sinusoidal oscillation pulseswith the frequencies f₁ to f₄. The individual sinusoidal oscillationpulses can in this case for example be combined in a linear or nonlinearfashion. This means that the sinusoidal oscillations with the individualfrequencies f₁ to f₄ need not necessarily be combined with the sameamplitudes in order to form the acoustic stimulation signal 15. Thefrequency spectrum of the acoustic stimulation signal 15 at fourdifferent times t₁, t₂, t₃ and t₄ is illustrated in the bottom row ofFIG. 10 in an exemplary fashion. The frequency spectra illustratedthere, more particularly the height and shape of the frequency peaks,should be understood to be merely exemplary and can also have completelydifferent shapes. In detail, the following statements can be gatheredfrom the illustrated frequency spectra: Only the frequency f₁ occurs inthe acoustic stimulation signal 15 at the time t₁. At the time t₂, theseare the frequencies f₃ and f₄; at the time t₃, these are the frequenciesf₂ to f₄; and at the time t₄, these are the frequencies f₂ and f₃.

According to an alternative refinement, four frequency mixtures with theboundaries f_(j) ^(lower) and f_(j) ^(upper) (j=1, 2, 3, 4) are usedinstead of the frequencies f₁ to f₄. There can be any number offrequencies in the range between f_(j) ^(lower) and f_(j) ^(upper) in afrequency mixture j.

According to a further alternative refinement, other functions are usedinstead of the rectangular functions in order to modulate the amplitudeof the sinusoidal oscillations, e.g. sinusoidal half-waves withfrequencies lower than f₁ to f₄. By way of example, it is furthermorefeasible for triangular pulses to be used as modulation functions. Sucha pulse can have a jump-like onset (from 0 to 1) and thereafter decreaseto 0, wherein the decrease can for example be given by a linear orexponential function. The modulation function ultimately determines theshape of the envelope of the individual pulses.

FIG. 11 illustrates the stimulation shown previously in FIG. 10 over arelatively long period of time. The individual sinusoidal oscillations,with the frequencies f₁=1000 Hz, f₂=800 Hz, f₃=600 Hz and f₄=400 Hz,have not been shown in FIG. 11, but only the respective rectangularenvelopes. Furthermore, FIG. 11 illustrates a measurement signal 24recorded by the measurement unit 23 for example, which measurementsignal reproduces the neuronal activity in the auditory cortex beforeand during the stimulation. In the present case, the period T_(stim) is1/(3.5 Hz)=0.29 s.

As shown in this example, the stimulation is started at the timet_(start). It can be gathered from the measurement signal 24, which hasbeen band-pass filtered in the present example, that the neurons in theauditory cortex have a synchronous and oscillatory activity before thestart of the stimulation. The pathologically synchronous neuronalactivity in the target area has already been suppressed shortly afterthe start of the stimulation.

There can be various deviations from the strictly periodic stimulationpattern shown in FIGS. 10 and 11. By way of example, the time delay τbetween two successive sinusoidal oscillation pulses need notnecessarily always be of the same magnitude. It should be understoodthat provision can be made for the time separations between theindividual sinusoidal oscillation pulses to be selected such that theydiffer. Furthermore, the delay times can also be varied during thetreatment of a patient. The delay times can also be adjusted in respectof the physiological signal run times.

Furthermore, in one refinement of the exemplary embodiment, pauses canbe provided during the application of the acoustic stimulation signal15, during which pauses there is no stimulation. The pauses can beselected to have any duration and more particularly are an integermultiple of the period T_(stim). The pauses can be held after any numberof stimulations. By way of example, a stimulation can be performed overN successive periods of length T_(stim), and there can subsequently be astimulation pause over M periods of length T_(stim), wherein N and M aresmall whole numbers, for example in the range between 1 and 15. Thisscheme can be either continued periodically or modified stochasticallyand/or deterministically, for example, chaotically.

FIG. 12 shows such a stimulation. Here N=2 and M=1 hold true. Otherwisethe stimulation corresponds to the stimulation shown in FIG. 11.

In one refinement, a further option for deviating from the strictlyperiodic stimulation pattern shown in FIG. 10 consists of stochastic ordeterministic or mixed stochastic-deterministic variation of the timeseparations between successive pulses with a frequency f_(j) or afrequency mixture with the boundaries f_(j) ^(lower) and f_(j) ^(upper)(j=1, 2, 3, 4).

Additionally, the order in which the involved frequencies f_(j) orfrequency mixtures with the boundaries f_(j) ^(lower) and f_(j) ^(upper)can be varied during each period T_(stim) (or during other time steps).Preferably, this variation can be stochastic or deterministic or mixedstochastic-deterministic.

Furthermore, it is possible for only a certain number of the frequenciesf_(j) or frequency mixtures with the boundaries f_(j) ^(lower) and f_(j)^(upper) to be applied in each period T_(stim) (or another timeinterval) and the frequencies f_(j) or frequency mixtures with theboundaries f_(j) ^(lower) and f_(j) ^(upper) involved in the stimulationcan be varied during each time interval. This variation can also bestochastic or deterministic or mixed stochastic-deterministic.

The above-described stimulation signals bring about a reset at differenttimes in the phase of the neuronal activity of the pathological neuronpopulation at the different stimulation sites. This splits thepathological neuron population, the neurons of which were previouslyactive in a synchronous fashion and with the same frequency and phase,into a plurality of sub-populations, which ultimately leads to adesynchronization.

In one embodiment, all stimulation forms described above can also beperformed in a “closed-loop” mode. Resetting the phases of theindividual sub-populations can for example be linked to a demand-drivencontrol. By way of example, a threshold can be prescribed and if theamplitude of the measurement signal 24 exceeds or drops below thethreshold the stimulation can be started or interrupted. Furthermore,certain stimulation parameters, such as the amplitude/strength of thestimulation signals or the duration of the stimulation, can be set onthe basis of the amplitude of the measurement signal 24, which can forexample be recorded during stimulation pauses. Moreover, it is possiblefor the frequency f_(stim) to be set or readjusted on the basis of themean frequency of the (possibly band-pass filtered) measurement signal24.

Moreover, it is feasible for the stimulation to be started by thepatient, for example by means of a telemetric activation. In this case,the patient can activate the stimulation for a prescribed period of time(e.g., 5 minutes) or the patient can independently start and stop thestimulation.

Herein below, further refinements of the “closed-loop” stimulation aredescribed, which can for example be performed by means of the device 400shown in FIG. 4 or one of the exemplary devices 600 to 900. As alreadydescribed previously, the measurement signal 24 recorded by themeasurement unit 23 can be used to generate a control signal 14, bymeans of which the stimulation unit 11 is actuated. Here, themeasurement signal 24 can be converted directly or if need be after oneor more processing steps into the acoustic stimulation signal 15 and canbe applied by the stimulation unit 11. Herein, the combination mode canbe selected such that the pathological neuronal activity is counteractedand the acoustic stimulation signal 15 likewise disappears or is atleast significantly reduced in its strength as the pathological neuronalactivity reduces.

In one embodiment, before the measurement signal 24 is fed into thecontrol input of the stimulation unit 11, the measurement signal 24 canbe processed in a linear or nonlinear fashion. By way of example, themeasurement signal 24 can be filtered and/or amplified and/or acted uponwith a time delay and/or mixed with another measurement signal 24.Furthermore, the measurement signal 24 or the processed measurementsignal 24 can modulate the amplitude of a sinusoidal oscillation with afrequency in the audible range and the amplitude-modulated sinusoidaloscillation can thereafter be applied as an acoustic stimulation signal15 or part thereof by means of the sound generator.

It should be noted that it is not necessary for the entire measurementsignal 24 to be used for modulating the amplitude of a sinusoidaloscillation or another oscillating oscillation. By way of example,provision can be made for only part of the measurement signal 24 or theprocessed measurement signal 24 to be used for this, for example, thepart lying above or below a particular threshold. Such an amplitudemodulation is illustrated in FIG. 13 in an exemplary fashion. Theuppermost graph in FIG. 13 plots the band-pass filtered measurementsignal 24 over time t; furthermore, the start time t_(start) of thestimulation is specified. The middle graph illustrates the modulationsignal 50 obtained from the measurement signal 24. The measurementsignal 24 has been processed in a nonlinear fashion and all negativevalues of the measurement signal 24 or the processed measurement signal24 have been set to zero in order to generate the modulation signal 50.Furthermore, the modulation signal 50 has a time delay compared to themeasurement signal 24. The half-wave signal 50 obtained in this fashionhas subsequently been multiplied with a sinusoidal oscillation at afrequency of f₁=1000 Hz. The modulation signal 50 constitutes theenvelope of the sinusoidal oscillation, as shown in the lowermost graphof FIG. 13 for a small time interval. The amplitude-modulated sinusoidaloscillation obtained thereby has subsequently been coupled back into thestimulation unit 11 in order to be converted into the acousticstimulation signal 15 by the sound generator.

Instead of a sinusoidal oscillation with a single frequency, themodulation signal 50 can also be multiplied by any mixture of sinusoidaloscillations (or other oscillations) in the audible frequency rangedepending on in which sites in the auditory cortex the desynchronizationshould be brought about.

It can be read out from the profile of the measurement signal 24illustrated in FIG. 13 that the acoustic nonlinear time-delayedhalf-wave stimulation leads to a robust suppression of thepathologically synchronous neuronal activity. However, the mechanism ofaction of this stimulation differs from the mode of operation of thestimulation method shown in e.g. FIG. 10. In the stimulation illustratedin FIG. 13, it is not the phase of the neuronal activity in therespectively stimulated sub-populations that is reset, but thesynchronization in the pathologically active neuron population issuppressed by influencing the saturation process of the synchronization.

The following text explains with the aid of an example how a measurementsignal 24 obtained by the measurement unit 20 can be subjected tononlinear processing before it is used as an actuation signal for thestimulation unit 11.

The start point is an equation for the actuation signal S(t):

s(t)=K·Z ²(t)· Z *(t−τ).   (1)

In equation (1), K is an amplification factor that can be selected in asuitable fashion and Z(t) is an average state variable of themeasurement signal 24. Z(t) is a complex variable and can be representedas follows:

Z (t)=X(t)+iY(t),   (2)

wherein X(t) can correspond to e.g. the neurological measurement signal24. Since the considered frequencies lie in the vicinity of 10 Hz=1/100ms=1/T_(α), the imaginary part Y(t) can be approximated by X(t−τ_(α)),wherein for example τ_(α)=T_(α)/4 holds true. This results in:

S(t)=K·[X(t)+iX(t−τ _(α))]² ·[X(t−τ)−iX(t−τ−τ _(α))].   (3)

Equation (3) can be rewritten as follows:

$\begin{matrix}{{S(t)} = {K \cdot {\left\lbrack {{{X(t)}^{2} \cdot {X\left( {t - \tau} \right)}} + {i\; 2{{X(t)} \cdot {X\left( {t - \tau_{\alpha}} \right)} \cdot {X\left( {t - \tau} \right)}}} - {{X\left( {t - \tau_{a}} \right)} \cdot {X\left( {t - \tau} \right)}} - {{{iX}\left( {t - \tau - \tau_{\alpha}} \right)} \cdot {X(t)}^{2}} + {2{{X(t)} \cdot {X\left( {t - \tau_{\alpha}} \right)} \cdot {X\left( {t - \tau - \tau_{\alpha}} \right)}}} + {{{iX}\left( {t - \tau - \tau_{\alpha}} \right)} \cdot {X\left( {t - \tau_{\alpha}} \right)}}} \right\rbrack.}}} & (4)\end{matrix}$

The real part of equation (4) is used as the actuation signal for thestimulation unit 11:

real[S(t)]=K·[X(t)² ·X(t−τ)−X(t−τ_(α))·X(t−τ)+2X(t)·X(t−τ _(α))·X(t−τ−τ_(α))]  (5)

The auditory cortex can furthermore be stimulated at different sites ina targeted fashion by using the fed-back and possibly further-processedmeasurement signal 24. In the case of the above-described four differentfrequencies f₁ to f₄, the possibly further-processed measurement signal24 is acted upon by an appropriate time delay and multiplied by thefrequencies f₁ to f₄. Provided that the stimulation is intended to beless focal and over a larger area, four different frequency mixtureswith the boundaries f_(j) ^(lower) and f_(j) ^(upper) (j=1, 2, 3, 4) areused instead of the pure sinusoidal oscillations at the frequencies f₁to f₄.

FIG. 14 illustrates such a stimulation in an exemplary fashion. Themodulation signals 51, 52, 53 and 54 have been obtained here from theband-pass filtered measurement signal 24 by means of linear processingsteps, by means of which modulation signals the amplitude of frequenciesf₁ to f₄ has been modulated. The control signal 14 has been generated bythe superposition of the modulated sinusoidal oscillations, whichcontrol signal has been converted into the acoustic stimulation signal15 by the sound generator 11.

Herein below, FIGS. 15A and 15B are used to explain in an exemplaryfashion how the modulation signals 51 to 54 can be obtained from themeasurement signal 24. For this, a delay time r is first of all fixed,which has been set to be τ=T_(stim)/2 in the present example (othervalues, such as τ=T_(stim) or τ=3T_(stim)/2, are likewise possible). Byway of example, the frequency f_(stim)=1/T_(stim) can lie in thevicinity of the mean frequency of the measurement signal 24, e.g. in therange between 1 and 30 Hz, more particularly in the range between 5 and20 Hz. Particular delay times τ₁, τ₂, τ₃ and τ₄ can be calculated foreach of the modulation signals 51 to 54 with the aid of the delay timeτ, for example with the aid of the following equation:

$\begin{matrix}{{\tau_{j} = {{{\tau \cdot \frac{11 - {2 \cdot \left( {j - 1} \right)}}{8}}\mspace{14mu} {with}\mspace{14mu} j} = 1}},2,3,4.} & (6)\end{matrix}$

By way of example, the modulation signals 51 to 54 can be obtained fromthe measurement signal 24 by the measurement signal 24 in each casebeing delayed by the delay times τ₁, τ₂, τ₃ and τ₄:

S _(j)(t)=K·Z(t−τ _(j)).   (7)

In equation (7), S₁(t), S₂(t), S₃(t) and S₄(t) represent the modulationsignals 51 to 54 and Z(t) represents the measurement signal 24. K is anamplification factor, which can be selected in a suitable fashion.Furthermore, all negative values (or all values above or below aparticular threshold) of the modulation signals S₁(t) to S₄(t) can beset to zero.

According to one refinement illustrated in FIGS. 15A and 15B, themodulation signals S₁(t) to S₄(t) are calculated from only the delaytimes τ₁ and τ₂, wherein the modulation signals S₁(t) and S₂(t), andS₃(t) and S₄(t) in each case have different polarities:

S ₁(t)=K·Z(t−τ ₁)   (8)

S ₂(t)=−K·Z(t−τ ₁)   (9)

S ₃(t)=K·Z(t−τ ₂)   (10)

S ₄(t)=−K·Z(t−τ ₂).   (11)

In FIGS. 15A and 15B the modulation signals S₁(t) and S₃(t) have beendisplaced upward by a value of 0.5 and the modulation signals S₂(t) andS₄(t) have been displaced downward by a value of 0.5 for the purpose ofa clearer illustration.

As shown in FIG. 15B, all negative values (or all values above or belowa certain threshold) of the modulation signals S₁(t) to S₄(t) can be setto zero. The generation of the modulation signals 51 to 54 shown in FIG.14 corresponds to the generation of the modulation signals S₁(t) toS₄(t) shown in FIGS. 15A and 15B. While the foregoing has been describedin conjunction with exemplary embodiments, it is understood that theterm “exemplary” is merely meant as an example, rather than the best oroptimal. Accordingly, the application is intended to cover alternatives,modifications and equivalents, which may be included within the spiritand scope of the disclosure herein.

Additionally, in the preceding detailed description, numerous specificdetails have been set forth in order to provide a thorough understandingof the present application. However, it should be apparent to one ofordinary skill in the art that the present device and method disclosedherein may be practiced without these specific details. In otherinstances, well-known methods, procedures, components, and circuits havenot been described in detail so as not to unnecessarily obscure aspectsof the present application.

1-18. (canceled)
 19. A neurological disease treatment device fordesynchronizing neuronal brain activity of a patient to treat tinnitus,the neurological disease treatment device comprising: an input operationunit configured to receive an input signal that defines parametersconfigured to set desynchronizing signals of the neuronal brain activityto treat the tinnitus; a stimulation unit configured to treat tinnitusof the patient by generating an acoustic stimulation signal comprising aplurality of acoustic tones including at least a first acoustic tone anda second acoustic tone that stimulate neuronal brain activity ofrespective neuron subpopulations when acoustically received by thepatient; and a controller configured to control the stimulation unit togenerate the acoustic stimulation signal based on measurement feedbackfrom the patient of the tinnitus and the defined parameters received bythe input operation unit, such that the first acoustic tone comprises afirst frequency or first frequency mixture in a first frequency rangeand the second acoustic tone comprises a second frequency or secondfrequency mixture in a second frequency range different from the firstfrequency range, wherein the controller is configured to control thestimulation unit to generate the acoustic stimulation signal includingthe plurality of acoustic tones in a repeated periodic sequence having astimulation frequency f_(stim) in a frequency range between about 1 Hzand 30 Hz.
 20. The neurological disease treatment device according toclaim 19, wherein the plurality of acoustic tones further comprises athird acoustic tone and a fourth acoustic tone, wherein the thirdacoustic tone comprises a third frequency or third frequency mixture ina third frequency range different from the first frequency range andfrom the second frequency range, and wherein the fourth acoustic tonecomprises a fourth frequency or fourth frequency mixture in a fourthfrequency range different from the first frequency range, from thesecond frequency range and from the third frequency range.
 21. Theneurological disease treatment device according to claim 20, wherein theplurality of acoustic tones are pure tones.
 22. The neurological diseasetreatment device according to claim 21, wherein the first frequency is600 Hz, the second frequency is 800 Hz, the third frequency is 400 Hzand the fourth frequency is 1000 Hz.
 23. The neurological diseasetreatment device according to claim 20, wherein each of the plurality ofacoustic tones is an oscillating signal with one of sinusoidaloscillations and rectangular oscillations.
 24. The neurological diseasetreatment device according to claim 23, wherein the controller isconfigured to modulate the oscillating signal by one of a rectangularpulse and a triangular pulse.
 25. The neurological disease treatmentdevice according to claim 20, wherein the stimulation unit is configuredto generate the acoustic stimulation signal with each acoustic toneoccurring with a time offset with respect to a previous acoustic tone ofthe plurality of acoustic tones.
 26. The neurological disease treatmentdevice according to claim 25, wherein the time offset between twosuccessive acoustic tones lies in a fourth of a stimulation periodT_(stim), with the stimulation period T_(stim) being equal to an inverseof the stimulation frequency F_(stim).
 27. The neurological diseasetreatment device according to claim 26, wherein the time offset deviatesup to 10%, or 20%, or 30%, respectively, from a value equal to thefourth of the stimulation period T_(stim).
 28. The neurological diseasetreatment device according to claim 20, wherein the stimulation unit isfurther configured to: generate the acoustic stimulation signal for Nsubsequent stimulation periods T_(stim), the stimulation period beingequal to an inverse of the stimulation frequency F_(stim), and notgenerate the acoustic simulation signal for M subsequent stimulationperiods T_(stim), wherein N and M are whole numbers in the range between1 and
 15. 29. The neurological disease treatment device according toclaim 19, wherein the input operation unit is configured to receive themeasurement feedback that control the parameters configured to setdesynchronizing signals of the neuronal brain activity to treat thetinnitus, and wherein the controller is further configured to controlthe stimulation unit to generate the acoustic stimulation signal basedon the measurement feedback to generate the acoustic stimulation signal.30. A neurological disease treatment device for treating a patient withtinnitus, the neurological disease treatment device comprising: astimulation unit configured to treat tinnitus of the patient bygenerating an acoustic stimulation signal comprising a plurality ofacoustic tones including at least first and second acoustic tones that,when acoustically received by the patient, stimulate respective neuronsubpopulation of the patient causing the tinnitus experienced by thepatient; and a controller configured to control the stimulation unit togenerate the acoustic stimulation signal based on measurement feedbackof the tinnitus experienced by the patient, such that the first acoustictone comprises a first frequency or first frequency mixture in a firstfrequency range and the second acoustic tone comprises a secondfrequency or second frequency mixture in a second frequency rangedifferent from the first frequency range, wherein the controller isconfigured to control the stimulation unit to generate the acousticstimulation signal including the plurality of acoustic tones in arepeated periodic sequence having a stimulation frequency f_(stim) in afrequency range between about 1 Hz and 30 Hz, such that the plurality ofacoustic tones are configured to treat the respective neuronsubpopulation causing the tinnitus.
 31. The neurological diseasetreatment device according to claim 30, further comprising: an inputoperation unit configured to receive a signal from the patientindicating the measurement feedback, and wherein the controller isfurther configured to control the stimulation unit to generate theacoustic stimulation signal based on the measurement feedback receivedby the input operation unit to treat the tinnitus experienced by thepatient.
 32. The neurological disease treatment device according toclaim 31, wherein the input operation unit comprises a measurementsensor configured to measure the measurement feedback of the tinnitusexperienced by the patient in response to the acoustic stimulationsignal.
 33. The neurological disease treatment device according to claim31, wherein the measurement feedback is configured to define theparameters configured to set desynchronizing signals of the neuronalbrain activity to treat the tinnitus.
 34. The neurological diseasetreatment device according to claim 30, wherein each of the plurality ofacoustic tones is an oscillating signal with one of sinusoidaloscillations and rectangular oscillations.
 35. The neurological diseasetreatment device according to claim 34, wherein the controller isconfigured to modulate the oscillating signal by one of a rectangularpulse and a triangular pulse.
 36. The neurological disease treatmentdevice according to claim 30, wherein the stimulation unit is configuredto generate the acoustic stimulation signal with each acoustic toneoccurring with a time offset with respect to a previous acoustic tone ofthe plurality of acoustic tones, and wherein the time offset between twosuccessive acoustic tones lies in a fourth of a stimulation periodT_(stim), with the stimulation period T_(stim) being equal to an inverseof the stimulation frequency F_(stim).
 37. The neurological diseasetreatment device according to claim 30, wherein the stimulation unit isfurther configured to: generate the acoustic stimulation signal for Nsubsequent stimulation periods T_(stim), the stimulation period beingequal to an inverse of the stimulation frequency F_(stim), and notgenerate the acoustic simulation signal for M subsequent stimulationperiods T_(stim), wherein N and M are whole numbers in the range between1 and
 15. 38. A neurological disease treatment method for treating apatient with tinnitus, the method comprising: generating, by astimulation unit configured to treat tinnitus of the patient, anacoustic stimulation signal comprising a plurality of acoustic tonesincluding at least first and second acoustic tones that, whenacoustically received by the patient, stimulate respective neuronsubpopulation of the patient causing the tinnitus experienced by thepatient; controlling, by a controller, the stimulation unit to generatethe acoustic stimulation signal based on measurement feedback of thetinnitus experienced by the patient, such that the first acoustic tonecomprises a first frequency or first frequency mixture in a firstfrequency range and the second acoustic tone comprises a secondfrequency or second frequency mixture in a second frequency rangedifferent from the first frequency range; controlling, by thecontroller, the stimulation unit to generate the acoustic stimulationsignal including the plurality of acoustic tones in a repeated periodicsequence having a stimulation frequency f_(stim) in a frequency rangebetween about 1 Hz and 30 Hz, such that the plurality of acoustic tonesare configured to treat the respective neuron subpopulation causing thetinnitus.